Pharmacokinetics of Doxorubicin in Patients with Lymphoproliferative Disorders after Infusion of Doxorubicin-Loaded Erythrocytes

  • Fazoil I. Ataullakhanov
  • Valentin G. Isaev
  • Alina V. Kohno
  • Elena V. Kulikova
  • Elena N. Parovichnikova
  • Valery G. Savchenko
  • Victor M. Vitvitsky

Abstract

Pharmacokinetics of doxorubicin infused as a solution or doxorubicin-loaded erythrocytes was studied in three patients with lymphoproliferative disorders. Homologous or autologous erythrocytes were loaded with doxorubicin aseptically by their incubation at 37°C in the solution of doxorubicin for 1 h. During the i.v. infusion of doxorubicin in solution (25–50 mg per square meter of body surface area), its concentration in blood rose to 3.60–5.90 ug/ml. Doxorubicin declined to about 0.1 ug/ml 20–30 min postinfusion and became zero 12–24 hours later. When these patients received the same doses of doxorubicin loaded into erythrocytes, doxorubicin in blood did not exceed 2.5 ug/ml. Within 10–30 min after the end of the infusion, doxorubicin decreased to about 0.1 ug/ml and remained at this level for 3 days and longer. Administrations of doxorubicin-loaded erythrocytes produced no adverse side effects.

Keywords

Lymphoproliferative Disorder Cytosine Arabinoside Anthracycline Antibiotic Human Erythro High Anticancer Activ 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ataullakhanov, F.I., Batasheva, T.V., Bukhman, V.M., Komarova, S.V., Oreshkina, T.D. and Vitvitsky, V.M. [1994] Treatment of Rausher virus induced murine erythroblastic leukemia with rubomycin loaded erythrocytes, in Carrier and Bioreactor Red Blood Cells for Drug Delivery and Targeting (DeLoach, J.R. and Way, J.L. eds.)., pp. 177–183. Elsevier Science Ltd, Oxford.Google Scholar
  2. 2.
    Ataullakhanov, F.I., Batasheva, T.V. and Vitvitsky, V.M. [1994] Influence of temperature, daunorubicin concentration and suspension hematocrit on daunorubicin binding by human erythrocytes. Antibiotiki i Chimioterapiya 39, No.9/10, 26-29 (in Russian).Google Scholar
  3. 3.
    Ataullakhanov, F.I., Batasheva, T.V., Vitvitsky, V.M. and Komarova, S.V. [1993] Effect of glutaraldehyde treatment on rubomycin and hemoglobin leakage from murine erythrocytes loaded with rubomycin. Biotekhnologiya, No. 2, 40-43 (in Russian).Google Scholar
  4. 4.
    Ataullakhanov, F.I., Kulikova, E.V. and Vitvitsky, V.M. [1994] Doxorubicin binding by human erythrocytes, in Carrier and Bioreactor Red Blood Cells for Drug Delivery and Targeting (DeLoach, J.R. and Way, J.L. eds.)., pp. 163–168. Elsevier Science Ltd, Oxford.Google Scholar
  5. 5.
    Ataullakhanov, F.I., Vitvitsky, V.M., Kovaleva, V.L. and Mironova, S.B. [1992] Rubomycin loaded erythrocytes in the treatment of mouse tumor P388, in The Use of Resealed Erythrocytes as Carriers and Bioreactors (Magnani, M. and DeLoach, J.R. eds.)., pp. 209–213. Plenum Press, New York.CrossRefGoogle Scholar
  6. 6.
    Benjamin, R.S., Riggs, C.E. and Bachur, N.R. [1977] Plasma pharmacokinetics of adriamycin and its metabolites in humans with normal hepatic and renal function. Cancer Res. 37, 1416–1420.PubMedGoogle Scholar
  7. 7.
    Cassiletti, P.A. and Katz, M.E. [1977] Chemotherapy for adult acute non lymphocytic leukemia with daunorubicin and cytosine arabinoside. Cancer Treat. Rep. 61, 1441–1445.Google Scholar
  8. 8.
    DeFlora, A., Benatti, U., Guida, L. and Zocchi, E. [1986] Encapsulation of doxorubicin in human erythrocytes. Proc. Natl. Acad. Sci. USA. 83, 7029–7033.CrossRefGoogle Scholar
  9. 9.
    Gaudreault, R.C., Bellemare, B. and Lacroix, J. [1989] Erythrocyte membrane-bound daunorubicin as a delivery system in anticancer treatment. Anticancer Res. 9, 1201–1205.PubMedGoogle Scholar
  10. 10.
    Gasparini, A., Tonetti, M., Astroff, B., Rowe, L., Satterfield, W., Schmidt, R. and DeLoach, J.R. [1992] Pharmacokinetics of doxorubicin loaded and glutaraldehyde treated erythrocytes in healthy and lymphoma bearing dogs, in The Use of Resealed Erythrocytes as Carriers and Bioreactors (Magnani, M. and DeLoach, J.R. eds.)., pp. 299–304. Plenum Press, New York.CrossRefGoogle Scholar
  11. 11.
    Kitao, T. and Hattori, K. [1980] Erythrocyte entrapment of daunomycin by amphotericin B without hemolysis. Cancer Res. 40, 1351–1353.PubMedGoogle Scholar
  12. 12.
    Kitao, T., Hattori, K. and Takeshita, M. [1978] Agglutination of leukemic cells and daunomycin entrapped erythrocytes with lectin in vitro and in vivo. Experientia 34, 94–95.PubMedCrossRefGoogle Scholar
  13. 13.
    Lee, Y.-T.N., Chan, K.K., Harris, P.A. and Cohen, J.L. [1980] Distribution of adriamycin in cancer patients. Tissue uptakes, plasma concentration after IV and hepatic IA administration. Cancer 45, 2231–2239.PubMedCrossRefGoogle Scholar
  14. 14.
    Lefrak, E.A., Pitha, J., Rosenheim, S. and Gottlieb, J.A. [1973] A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 32, 302–314.PubMedCrossRefGoogle Scholar
  15. 15.
    Matherne, CM., Satterfield, W.C., Gasparini, A., Tonetti, M., Astroff, A.B., Schmidt, R.D., Rowe, L.D. and DeLoach, J.R. [1994] Clinical efficacy and toxicity of doxorubicin encapsulated in glutaraldehydetreated erythrocytes administered to dogs with lymphosarcoma. Am. J. Vet. Res. 55, 847–853.PubMedGoogle Scholar
  16. 16.
    Rachman, A., Fumagalli, A., Barbieri, B., Schein, P. and Casazza, A.M. [1986] Antitumor and toxicity evaluation of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes. Cancer Chemother. Pharmacol. 16, 22–27.Google Scholar
  17. 17.
    Satterfield, W.C., Matherne, CM., Clarke, M.S. and DeLoach, J.R. [1992] Clinical evaluation of glutaraldehyde-treated canine erythrocytesin normal dogs, in The Use of Resealed Erythrocytes as Carriers and Bioreactors (Magnani, M. and DeLoach, J.R. eds.)., pp. 319–324. Plenum Press, New York.CrossRefGoogle Scholar
  18. 18.
    Stenberg, C.P., Civin, C, Krischer, J., Culbert, S., Ragab, A., Ruymann, F.B., Ravindranath, J., Leventhal, B., Wilkinson, R. and Vietti, T.J. [1991] A comparison of induction and maintenance therapy for acute non-lymphocytic leukemia in childhood: results of a pediatric oncology group study. J. Clin. Oncol. 9, 247–288.Google Scholar
  19. 19.
    Tonetti, M., Astroff, B., Satterfield, W., DeFlora, A., Benatti, U. and DeLoach, J.R. [1990] Construction and characterization of adriamycin-loaded canine red blood cells as a potential slow delivery system. Biotechnol. Appl. Biochem. 12, 621–629.PubMedGoogle Scholar
  20. 20.
    Tonetti, M., Zocchi, E., Guida, Z., Polvani, C, Benatti, U., Biassoni, P., Romei, F., Guglielmi, A., Aschele, C, Sobrero, A. and DeFlora, A. [1992] Use of glutaraldehyde treated autologous human erythrocytes for hepatic targeting of doxorubicin, in The Use of Resealed Erythrocytes as Carriers and Bioreactors (Magnani, M. and DeLoach, J.R. eds.)., pp. 307–317. Plenum Press, New York.CrossRefGoogle Scholar
  21. 21.
    Zocchi, E., Tonetti, M., Polvani, C, Guida, Z., Benatti, U. and DeFlora, A. [1988] In vivo liver and lung targeting of adriamycin encapsulated in glutaraldehyde-treated murine erythrocytes. Biotechnol. Appl. Biochem. 10, 555–562.PubMedGoogle Scholar
  22. 22.
    Zocchi, E., Tonetti, M., Polvani, C, Guida, Z., Benatti, U. and DeFlora, A. [1989] Encapsulation of doxorubicin in liver-targeted erythrocytes increases the therapeutic index of the drug in murine metastatic model. Proc. Natl. Acad. Sci. USA. 86, 2040–2044.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Fazoil I. Ataullakhanov
    • 1
  • Valentin G. Isaev
    • 1
  • Alina V. Kohno
    • 1
  • Elena V. Kulikova
    • 1
  • Elena N. Parovichnikova
    • 1
  • Valery G. Savchenko
    • 1
  • Victor M. Vitvitsky
    • 1
  1. 1.Scientific Center for Hematology of RAMSMoscowRussia

Personalised recommendations